TY - JOUR
T1 - Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins
T2 - A pilot prospective, randomized, controlled study
AU - Ladenson, Paul W.
AU - McCarren, M.
AU - Morkin, E.
AU - Edson, R. G.
AU - Shih, Mei Chiung
AU - Warren, S. R.
AU - Barnhill, J. G.
AU - Churby, L.
AU - Thai, H.
AU - O'Brien, T.
AU - Anand, I.
AU - Warner, A.
AU - Hattler, B.
AU - Dunlap, M.
AU - Erikson, J.
AU - Goldman, S.
N1 - Funding Information:
Disclosure Summary: S.G. previously owned stock in Titan. S.G., E.M., and P.W.L. were consultants for Titan but no longer receive payments. P.W.L. previously received grant support from Titan. The first U.S. patent application for DITPA was issued as US 6,534,676 on March 18, 2003. The Canadian counterpart is CA 2002243801, which was issued on March 22, 2007. A second U.S. patent application for analogs of DITPA was issued as US 6,716,877 on April 6, 2004. S.G., E.M., Gregory Pennock, and Joseph Bahl received a use patent for DITPA (U.S. Patent 6,534,676 B2 UA no. 03-075) that was assigned to the University of Arizona. The Department of Veterans Affairs and the University of Arizona have an agreement regarding the management of co-owned inventions and/or intellectual property that enables the university to direct matters related to patenting, marketing, and licensing of co-owned inventions. The University of Arizona licensed DITPA to Titan Pharmaceutical (South San Francisco, CA). In December 2008, Titan Pharmaceutical discontinued its development of DITPA, and the license has reverted to the University of Arizona.
PY - 2010/3
Y1 - 2010/3
N2 - Context: Widespread thyroid hormone actions offer the possibility of developing selective thyromimetic analogs with salutary metabolic properties. Consequently, effects of diiodothyropropionic acid (DITPA) on body weight, serum lipoproteins, and bone metabolism markers were studied in a prospective, controlled, double-blind 24-wk trial, which was primarily designed to assess treatment of stable chronic heart failure. Design: Eighty-six patients (aged 66 ± 11 yr, mean ± SD) were randomized (1:2) to placebo or an escalating DITPA dose (90 to 180, 270, and 360 mg/d) over 8 wk until serum TSH was less than 0.02 mU/liter. Patients were studied at 2, 4, 6, 8, 16, and 24 wk and after 4 wk off study drug. Only 21 DITPA-treated and 27 placebo patients completed the full 24 wk of therapy. Results: DITPA therapy lowered serum TSH levels and, to a lesser extent, serum T3 and T4, buttherewere no differences in clinical manifestations of thyrotoxicosis or hypothyroidism. Serum total and lowdensity lipoprotein cholesterol levels both decreased on DITPA; there was a transient decrease in triglycerides andnochange in high-density lipoprotein cholesterol. DITPA therapy was associated with significant reduction in body weight, 12.5 lb at 24 wk. Increases in serum osteocalcin, N-telopeptide, and deoxypyridinoline levels were consistent with increased bone turnover on DITPA. Conclusion: This investigation of DITPA actions demonstrated its efficacy in reducing body weight andlowering totalandlow-density lipoprotein cholesterol levels. However, DITPA's adverse effects at doses used resulted in a high dropout rate and potentially dangerous skeletal actions were observed.
AB - Context: Widespread thyroid hormone actions offer the possibility of developing selective thyromimetic analogs with salutary metabolic properties. Consequently, effects of diiodothyropropionic acid (DITPA) on body weight, serum lipoproteins, and bone metabolism markers were studied in a prospective, controlled, double-blind 24-wk trial, which was primarily designed to assess treatment of stable chronic heart failure. Design: Eighty-six patients (aged 66 ± 11 yr, mean ± SD) were randomized (1:2) to placebo or an escalating DITPA dose (90 to 180, 270, and 360 mg/d) over 8 wk until serum TSH was less than 0.02 mU/liter. Patients were studied at 2, 4, 6, 8, 16, and 24 wk and after 4 wk off study drug. Only 21 DITPA-treated and 27 placebo patients completed the full 24 wk of therapy. Results: DITPA therapy lowered serum TSH levels and, to a lesser extent, serum T3 and T4, buttherewere no differences in clinical manifestations of thyrotoxicosis or hypothyroidism. Serum total and lowdensity lipoprotein cholesterol levels both decreased on DITPA; there was a transient decrease in triglycerides andnochange in high-density lipoprotein cholesterol. DITPA therapy was associated with significant reduction in body weight, 12.5 lb at 24 wk. Increases in serum osteocalcin, N-telopeptide, and deoxypyridinoline levels were consistent with increased bone turnover on DITPA. Conclusion: This investigation of DITPA actions demonstrated its efficacy in reducing body weight andlowering totalandlow-density lipoprotein cholesterol levels. However, DITPA's adverse effects at doses used resulted in a high dropout rate and potentially dangerous skeletal actions were observed.
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U2 - 10.1210/jc.2009-1209
DO - 10.1210/jc.2009-1209
M3 - Article
C2 - 20080837
AN - SCOPUS:77749270649
VL - 95
SP - 1349
EP - 1354
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 3
ER -